The identification of tumor-associated antigens recognized by a mammalian immune system is useful for the diagnosis and treatment of cancer. A variety of tumor-associated antigens have been identified, including cancer/testis antigens that are expressed in cancer cells, but not in normal tissues other than testis. Only a minority of tumor-associated antigens, however, are immunogenic to the mammal that produces them.
BORIS (Brother of the Regulator of Imprinted Sites) is a tumor-associated antigen, which is activated in a wide range of human cancers. In fact, aberrant synthesis of the BORIS gene product has been found in over 300 primary tumors and cancer cell lines representing all major types of human cancers with recurrent 20q13 chromosomal gains. BORIS activation has also been found in all of the standard NCI-60 cancer cell lines, which are maintained by the National Cancer Institute (NCI), and which are thought to be a reasonably complete representative set of human cancers. One mechanism of action by which BORIS is thought to cause cancer through interference with the maintenance of an appropriate methylation pattern in the genome mediated by CCCTC binding factor (CTCF) (see Klenova et al., Seminars in Cancer Biology 12, 399-414 (2002)).
BORIS is also a CTCF paralog, which contains all eleven zinc fingers of CTCF, and has been shown to promote cell growth leading to transformation (see Loukinov et al, Proc. Natl. Acad. Sci. (USA) 99, 6806-6811 (2002), and International Patent Application Publication WO 03/072799 (PCT/US03/05186)). The BORIS gene is believed to map to the cancer-associated amplification region of chromosome 20q13.
The detection of aberrant expression of cancer markers, such as prostate specific antigen (PSA) and carcinoembryonic antigen (CEA), are known in the art. These assays, however, detect only a limited number of cancers, and have limited positive predictive value for the detection of new or recurring cancer, or for the prognosis of cancer. Accordingly, there is a need in the art to identify additional antigens whose expression can be linked to hyperproliferative diseases, such as cancer, as well as methods of detecting the presence of such antigens to aid in the detection, diagnosis, prognostication, or research of such disease states.
The invention provides methods and compositions useful for the detection, diagnosis, prognostication, or research of diseases associated with abnormal BORIS expression, such as cancer. These and other advantages of the invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.